DAVID CAMERON, MB ChB,
MPraxMed, MPhil (Pall Med), FCFP (SA)

Associate Professor, Department of Family
Medicine, University of Pretoria and Senior Consultant, Foundation for Professional
Development

It is usually possible to deal with severe pain in patients with
advanced cancer by following basic palliative care principles.
Occasionally, however, a patient whose pain had previously been well
controlled suddenly starts experiencing pain again.

‘Doctor, my pain is getting worse. Please help me.’ This
is a real challenge for any doctor. Consider the following possible
reasons for this change:1-7

• The disease has progressed. The appropriate response would be to increase the dose of the analgesics.

• Coping with cancer is challenging. At times the
patient’s ability to manage is overwhelmed and this distress is
expressed in excessive somatic complaints that have no organic basis.
Somatisation needs careful exploration rather than more analgesia.7

• The patient has developed pharmacological tolerance to the
dose of their current analgesics and the dose should be adjusted.1-3,7

• The previous reduction in pain has allowed the patient to be
more active and the current dose is too low for such additional
physical activity. This patient needs a more flexible regimen to allow
for incidental activity.1,2

Let us imagine that you have explored the patient’s emotional
state and you decide the increased pain is not due to somatisation.
Careful examination reveals no evidence of further disease progression.
So you decide that the patient has developed pharmacological tolerance
and you increase the dose of the opioid analgesic by 30% as recommended
by the palliative care consultant, Dr Mary Smith, whose lecture you
attended last week.

The next day, much to your surprise, things have deteriorated.
‘Mr Jones is not well today,’ says Sr Margaret, ‘he
has become very drowsy. The night staff reported that he was restless
and complaining of strange animals in his room’. As you examine
Mr Jones you notice brief, irregular jerking of the muscles of his
right arm. There is also twitching of his facial and abdominal muscles.
He grimaces even when you touch him lightly. ‘You’ve got to
help me, doc. This pain is unbearable.’

What’s going on now? You did what the expert advised and now
things are worse. Fortunately you have the consultant’s emergency
number. You call and explain the situation. ‘It’s the
paradoxical pain of opioid-induced neurotoxicity (OIN) with
hyperalgesia,’ Dr Smith replies. She goes on to explain that
although morphine does not have the limitation of a maximum dose like
many other analgesics, sometimes OIN occurs. In some individuals,
particularly in the context of mild dehydration or deteriorating renal
function, there is a build-up of morphine metabolites, especially
morphine-3-glucuronide. These metabolites bind to the mµ
receptors and block the analgesic effect of morphine. In addition they
stimulate the nervous system and cause myoclonic jerking, confusion and
hallucinations. Sensitivity to light touch, allodynia, is another
feature of OIN.1-7

‘That’s fascinating but what do I do now?’ you
ask, ‘Should I give naloxone to reverse the condition?’ Dr
Smith calmly responds ‘No, that would just make things worse as
you would precipitate an acute opioid withdrawal syndrome with severe
pain and even convulsions’.7

‘Here is what you can do,’ continues Dr Smith:1-7

• ‘Reduce the morphine by 50% or change to a fentanyl
patch. This will allow the kidneys to gradually clear the morphine
metabolites without leaving Mr Jones in agony. Another alternative
would be to use sublingual buprenorphine every 8 hours. It’s a
pity we don’t have methadone available here as that also works
well in this situation.1,4

• ‘Encourage adequate hydration. If he cannot drink
enough oral fluids, you could give 1 litre of normal saline by
subcutaneous infusion (hypodermoclysis) over 24 hours.7
This is a simple procedure. Insert a butterfly needle into the
subcutaneous tissues on Mr Jones’s abdomen and attach the IV
solution to it. This is far less troublesome than an IV line and you
won’t get called out at 2 am to re-site an IV cannula.

• ‘If Mr Jones is not already on paracetamol, add 1 gm 6
hourly orally but avoid non-steroidal anti-inflammatory drugs as they
may aggravate the condition. If you get desperate, dexamethasone has
been recommended in the literature.2 Personally I have never found that necessary yet as OIN usually settles down over a day or so.’6

The next day Mr Jones is all smiles: he is eating and drinking well.
He is looking forward to watching the World Cup rugby final on
Saturday. You are pleased that everything has turned out well but there
is obviously more to learn about good palliative care and you decide to
register for the Diploma in Palliative Medicine at the University of
Cape Town with Dr Liz Gwyther.